Advancing Care for OCD: From Laboratory to Clinic

Lab research and clinical work are different, yet complimentary, approaches to mental health research. According to Christopher Pittenger, MD, PhD, when these approaches come together, researchers can build connections across findings that may appear inconsistent at first glance.

Dr. Pittenger is the director of the Yale OCD Research Clinic, where he and his team treat patients. He also runs a research lab at Abraham Ribicoff Research Facilities. By combining clinical work with patients with obsessive-compulsive disorder (OCD) with lab-based research using sophisticated molecular techniques, Pittenger aims to better understand the mechanisms of the brain that cause OCD. Ultimately, he hopes his research will lead to the development of better treatment options for patients.

OCD is a psychiatric disorder characterized by obsessions and compulsions. Obsessions are repeated thoughts that cause anxiety and distress. Obsessions are often characterized by fear of impending harm to one’s self or to a loved one; concern with becoming contaminated or contaminating others; or a need to do things correctly or perfectly. While many patients are aware that their thoughts are irrational, the nature of the disorder makes it impossible for them to quell their obsessions.

Patients with OCD respond to their obsessions with repetitive behaviors called compulsions. Common compulsions include checking and washing, repeating, hoarding and rearranging. Through compulsive behaviors, patients find temporary relief from their obsessions, but their anxiety will not go away.

OCD exists on a spectrum of varying severity. The disorder dramatically constricts what people can do in daily life, school, work, and at home. First-line treatments include cognitive behavior therapy, drug therapy with selective serotonin reuptake inhibitors (SSRIs), or both. Remission is rare; about one-third of patients do not experience substantial symptom reduction.

Pittenger’s lab is currently looking at the role of glutamate—a key compound in cellular metabolism—in OCD.

“From previous work, we know that glutamate is out of balance in patients with OCD,” explains Pittenger. However, the presence of abnormally high levels of glutamate in the brains of individuals with OCD does not necessarily prove that it contributes to the disease. Glutamate imbalance could be a consequence, rather than a cause, of illness.

This is where the lab comes in. Through sophisticated investigations in model systems, Pittenger and his team are developing more refined ideas about how and why glutamate might be out of balance.

“In the lab setting, we are able to ask more specific questions. Through better understanding of the biology, we can identify fundamentally new approaches to treatment,” said Pittenger.

According to Dr. Pittenger, there is a huge incentive in the field of psychiatry to be an expert in one area of research. With this approach, researchers can miss out on important work being done outside of their realm of expertise. Pittenger and his team use clinical work to identify interesting questions, which are translated to answerable questions worth asking in the lab setting.

Translational research, or translational science, promotes the application of research to the population under study.

When compared to questions formed during clinical research, questions about molecules, cells and model systems offer a very different, yet complimentary, approach. Collaboration between lab researchers and clinicians has the potential to transform the field and benefit patients. “The absolute amount of what we know about the brain is huge,” said Dr. Pittenger, “but this is only a small fraction of what we need to know.”

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